The incidence of oesophageal and gastro-oesophageal junctional (GOJ) adenocarcinoma has increased 6 fold in the last 30 years, making to it the commonest esophageal malignancy in the western world1. Unfortunately five year survival remains less than 8% for all patients diagnosed1 and only 18-23% for patients undergoing surgery2. It is staged using the internationally recognized TNM system3, although this has limited ability to stratify patients according to their likely outcome. While patients with advanced stage tumors clearly do worse than those with earlier disease, most patients present late (T3N1) and even within this group there are wide variations in survival. The highly invasive nature of esophageal surgery and the toxic nature of neoadjuvant regimes make it important to find better ways to select treatment. Complex management decisions require more accurate prognostic information. In other epithelial tumors molecular signatures have proven to be prognostic. In breast cancer gene signatures have been shown to predict survival4, 5 and response to chemotherapy6 with good external validation7, 8. In general while the breast cancer prognostic signatures have been well validated the same is not true of most molecular predictors of outcome. No molecular signatures have been incorporated into formal TNM staging, though some have gained a place in national cancer guidelines9. It has been proposed that a biomarker of prognosis should be sensitive, specific, cost effective, fast, robust against variability and better than current clinical parameters10. The US FDA and National Institute of Standards and Technology (NIST) have proposed five steps of biomarker validation; preclinical exploration, clinical assay and validation, retrospective longitudinal validation, prospective validation and demonstration of benefits in cancer outcomes11, 12. Other reviews looking at predictors of outcome have reiterated the need for external validation and the development of a test that has general clinical applicability13-16, while the REMARK guidelines suggested the requirements for reporting prognostic biomarker studies17.
While work continues to better stratify oesophageal and GOJ adenocarcinomas by more detailed characterization of clinical and pathological features18, 20, there remains a need in the art to prepare a robust and practical method and kit to aid in the prognosis of oesophageal and GOJ adenocarcinomas